The overall objective of the proposed study is to define the role of the mammalian immune response in protection against the nematode parasite Trichinella spiralis. Utilizing the murine model of T. spialis infection, three interrelated questions have been posed: 1. What is the role of immune lymphoid cells and sera in the alteration of specific resistance that develop during the course of chronic murine trichinosis? 2. What is the role of host granulocytes and complement in elimination of the various stages of T. spiralis in vivo and in vitro? 3. What are the subcellular and molecular mechanisms by which these calls and serum factors effect the destruction of T. spiralis? These questions will be answered by a sequece of in vivo and in vitro studies. The role of host immune cells and sera in altering specific resistance will be studied with passive transfer technics. Fractionation of the lymphoid cells into T-enriched and T-depleted populations will permit definition of the function of these cells in the modulation of resistance. The specific granulocytes and serum factors that effect the destruction of T. spiralis in the intact host will be identified by depletion of these components with monospecific anti-eosinophil and -neutrophil serum and cobra venom factor. The interaction of cellular and humoral factors in the host effector mechanism will be more fully defined and characterized with a recently developed in vitro model of eosinophil-mediated antibody-dependent newborn larval destruction. The cytotoxic effect of genetically mutant granulocytes will be compared with that of normal granulocytes in some of these studies. Finally, the subcellular and molecular basis of the parasite cytotoxic effect of eosinophils and neutrophils will be elucidated by the application of technics capable of measuring the release of minute quantities of lysosomal enzymes and highly reactive products of oxygen reduction.